Since recent evidence indicates that the pulmonary perivascular mast cell is an important regulator of the normal pulmonary vascular responses to hypoxia, through humoral agents which it releases, this study proposes to investigate the anatomy and physiological function of this cell under normal conditions and a variety of pathological circumstances where present evidence indicates this response may be deranged: For instance, experience recently gained in the histological evaluation of mast cell distribution and granulation will be used to study post mortem lungs 1) in diseases where the pulmonary pressor response to hypoxia is chronically operative, i.e., chronic obstructive lung disease, 2) in diseases where the pressor response to hypoxia has been demonstrated or suspected to be impaired, i.e., hepatic cirrhosis and familial dysautonomia, respectively, and 3) in a situation where products of sudden mast cell degranulation, viz., histamine, are suspected to be agents which acutely damage pulmonary blood vessels, i.e., heroin-induced pulmonary edema. In addition, this form of anatomic study will be furthered in the normal human and animal lung to determine the distribution of perivascular mast cell and, in whole animal and in vivo and in vitro preparations, physiological studies will be carried on to determine the effects of a variety of potential mast cell stimulators, such as hypercapnia, and to determine the manner, identity and function of the humoral agents released from mast cells.